Global epidemiology of liver cancer 2022: An emphasis on geographic disparities

Abstract

Background:

Liver cancer remains the sixth most commonly diagnosed cancer and the third leading cause of cancer-related deaths worldwide, causing a heavy burden globally. An updated assessment of the global epidemiology of the liver cancer burden that addresses geographical disparities is necessary to better understand and promote healthcare delivery.

Methods:

Data were extracted from the GLOBOCAN 2022 database, including the number, crude, and age-standardized rates of incidence and mortality at the global, country, continent, and human development index (HDI) regional levels. Age-standardized rates (incidence and mortality) per 100,000 person-years were adjusted based on the Segi-Doll World standard population. The mortality-to-incidence ratios (MIR) for each region and country were calculated. The HDI and gross national income (GNI) for 2022 were obtained, and a Pearson correlation analysis was conducted with the incidence, mortality, and MIR.

Results:

In 2022, approximately 866,136 new liver cancer cases and 758,725 related deaths were recorded worldwide, with a global MIR of 0.86. Males had a disproportionately higher burden than females across all levels, and the highest burden was observed in the elderly population. Geographically, the regions with the highest incidence rates included Micronesia, Eastern Asia, and Northern Africa, and the regions with the highest mortality rates included Northern Africa, Southeastern Asia, Eastern Asia, and Micronesia. Notably, Mongolia had a strikingly high burden compared to other countries. The highest MIR was observed in North America and the lowest in Africa. Negative associations of HDI and GNI with liver cancer mortality and MIR were identified, irrespective of sex.

Conclusions:

The current liver cancer burden underscores the presence of remarkable geographic heterogeneity, which is particularly evident across countries with varying HDI levels, highlighting the urgent need to prioritize health accessibility and availability to achieve health inequities.

Introduction

Primary liver cancer remains a global public health concern. It is the sixth most commonly diagnosed cancer and third leading cause of cancer-related deaths worldwide.^[1] Large variations in liver cancer burden have been observed across countries with varying levels of development. Remarkably, liver cancer is among the top five leading cancers in terms of mortality across the human development index (HDI).^[1] It is more common in sub-Saharan Africa and East Asia than in Western countries. The epidemiology of liver cancer in Asia has changed over the past few decades.^[2] In some Eastern Asian countries such as China, Japan, and the Republic of Korea, the incidence and mortality rates have decreased. In countries where liver cancer was previously less common, such as the United States, Australia, and several European countries, liver cancer rates have gradually increased.^[3]

These disparities vary markedly by geographic region and mainly result from heterogeneous risk factors and etiologies. Major risk factors for liver cancer include viral infections and lifestyle risk factors such as tobacco use, alcohol consumption, metabolic factors, and aflatoxins.^[4] Success in viral hepatitis prevention and treatment programs, effective surveillance of at-risk populations, and timely management of liver cancer cases at different stages underscore imperative priorities for improving the prognosis of liver cancer.^[5,6] Despite ongoing efforts, addressing the global burden of liver cancer remains challenging. Although many countries have implemented screening, treatment, and prevention programs targeting predominant risk factors, the effectiveness and equitable distribution of these interventions remain areas of concern.^[7] Moreover, projections suggest that, without substantial changes, the annual global number of new cases and deaths from liver cancer is expected to increase by more than 50% from 2020 to 2040.^[3] Socioeconomic determinants also contribute to these disparities.^[8] Income, health insurance, education, and living environment significantly affect liver cancer survival rates and prognostic outcomes to varying degrees as disparities persist between and within countries.^[9–11] Addressing the socioeconomic health determinants deserves to be paid more attention as it represents an essential area for improvement in terms of healthcare inequity.

To better understand the epidemiological landscape of liver cancer, a reassessment of the worldwide impact of liver cancer is imperative because of the disparities in its burden among different populations and the availability of more recent data. This study aimed to provide a comprehensive overview of liver cancer epidemiology, focusing on assessing geographic disparities worldwide at the country, continent, and HDI region levels, using the latest GLOBOCAN database. Our objective was to provide an up-to-date overview of the global liver cancer burden, highlighting effective prevention and control strategies.

Methods

Data sources

Data, including the number of cases, crude rates, age-standardized rates of incidence, and mortality from liver cancer at the global, country, continent, and HDI regional levels, were extracted from the GLOBOCAN 2022 database. The GLOBOCAN 2022 database, maintained by the International Agency for Research on Cancer, contains comprehensive statistics on 36 cancer types from 185 countries or territories, categorized by sex and age groups. The methods used to compile cancer estimates have been described previously in detail.^[12] The age-standardized rates (for both incidence and mortality) per 100,000 person-years were adjusted using the 1966 Segi-Doll World standard population.^[1] The diagnosis code for liver cancer was C22 (including intrahepatic bile ducts), which was defined based on the International Classification of Diseases 10th revision (ICD-10).

HDI and gross national income (GNI) per capita data for 2022 were obtained from the United Nations Development Program’s Human Development Report (https://hdr.undp.org). The HDI serves as a composite index for assessing human development across three dimensions: longevity, education, and standard of living. The value of the HDI ranges from 0 to 1, with 1 representing the highest attainable level of human development. The GNI measures a nation’s socioeconomic status and reflects the overall economic health and living standards of its population. This indicator, measured in terms of purchasing power parity, covers the total value added by all resident producers.^[13]

Statistical analysis

A comprehensive descriptive analysis of the incidence and mortality rates of liver cancer, stratified by geographic categories such as world regions, continents, and HDI levels, was conducted. In addition, the percentage contribution of each component to the global total was calculated. HDI regions were further classified into four subgroups, including countries with very high, high, medium, and low HDI, according to a predefined category. Distribution by sex was explored using the male-to-female ratio (M:F) and age groups (divided into three groups: 0–49 years, 50–74 years, and ≥75 years). The mortality-to-incidence ratio (MIR) was calculated as the mortality rate divided by the incidence rate, serving as an indicator of cancer outcomes and cancer control efficacy and a valid proxy for cancer survival.^[14] To assess potential associations, Pearson’s correlation analyses were employed between the incidence, mortality, and MIR with the HDI and GNI. Correlation coefficients (r) were calculated as statistics of association strength and significance was assessed using the non-parametric Spearman’s correlation test (P value <0.05). All statistical analyses and graphing were performed using the R software (version 4.3.2, R Foundation for Statistical Computing, Vienna, Austria).

Results

Liver cancer incidence, mortality, and MIR in 2022, worldwide

By 2022, 866,136 new liver cancer cases were estimated worldwide, including 265,460 females and 600,676 males [Table 1]. The age-standardized incidence rates (ASIR) were 8.6 per 100,000 for all, 4.8 per 100,000 for females, and 12.7 per 100,000 for males. Males had a much higher burden than females, accounting for approximately 69.35% of the total cases. Almost 49.96% of all liver cancer cases occurred in East Asia. The highest ASIRs were recorded in Micronesia (15.1 per 100,000), Eastern Asia (14.7 per 100,000), and Northern Africa (14.2 per 100,000).

Table 1.

Estimated incidence, mortality, and MIR of liver cancer by sex, world region, and HDI, in 2022.

Parameters	New cases	Incidence (per 100,000)		Percent (%)	Liver cancer-related death cases	Mortality (per 100,000)		Percent (%)	Mortality-to-incidence ratio
		Crude rate	ASR (World)			Crude rate	ASR (World)		Crude rate	ASR (World)
Worldwide	866,136	11.0	8.6	100	758,725	9.6	7.4	100	0.87	0.86
Sex
Female	265,460	6.8	4.8	30.65	236,899	6.1	4.1	31.22	0.90	0.85
Male	600,676	15.1	12.7	69.35	521,826	13.1	10.9	68.78	0.87	0.86
Region
Northern America	48,485	13.0	6.7	5.60	35,075	9.4	4.4	4.62	0.72	0.66
Eastern Asia	432,684	26.7	14.7	49.96	363,514	22.5	11.9	47.91	0.84	0.81
Eastern Africa	12,786	2.7	4.8	1.48	11,964	2.6	4.6	1.58	0.96	0.96
Middle Africa	7618	4.0	7.3	0.88	7247	3.8	7.1	0.96	0.95	0.97
Northern Africa	32,005	12.6	14.2	3.70	30,778	12.1	13.7	4.06	0.96	0.96
Southern Africa	2829	4.1	4.7	0.33	2575	3.7	4.3	0.34	0.90	0.91
Western Africa	18,606	4.4	7.9	2.15	17,751	4.2	7.7	2.34	0.95	0.97
Caribbean	3595	8.2	5.9	0.42	3134	7.1	4.9	0.41	0.87	0.83
Central America	12,917	7.0	6.4	1.49	11,769	6.4	5.8	1.55	0.91	0.91
South-Eastern Asia	103,629	15.2	13.5	11.96	99,733	14.6	13.0	13.14	0.96	0.96
South Central Asia	59,663	2.9	3.0	6.89	56,780	2.8	2.9	7.48	0.97	0.97
Western Asia	11,385	4.0	4.3	1.31	10,901	3.8	4.1	1.44	0.95	0.95
Eastern Europe	24,719	8.5	4.2	2.85	23,504	8.1	3.9	3.10	0.95	0.93
Northern Europe	12,334	11.5	4.7	1.42	11,048	10.3	3.9	1.46	0.90	0.83
Southern Europe	24,503	16.2	6.2	2.83	20,854	13.8	4.7	2.75	0.85	0.76
Western Europe	27,315	13.9	5.5	3.15	23,685	12.0	4.3	3.12	0.86	0.78
Australia-New Zealand	3715	12.0	6.7	0.43	2927	9.5	4.5	0.39	0.79	0.67
Melanesia	948	8.2	11.5	0.11	913	7.9	11.1	0.12	0.96	0.97
South America	26,257	6.0	4.4	3.03	24,448	5.6	4.0	3.22	0.93	0.91
Micronesia	90	16.1	15.1	0.01	73	13.0	11.9	0.01	0.81	0.79
Polynesia	53	7.7	6.9	0.01	52	7.5	6.8	0.01	0.97	0.99
HDI*
Very high HDI	239,368	14.6	7.1	27.64	196,390	12.0	5.4	25.88	0.82	0.76
High HDI	495,705	18.0	12.3	57.23	438,036	15.9	10.7	57.73	0.88	0.87
Medium HDI	91,923	4.1	4.3	10.61	86,943	3.8	4.1	11.46	0.93	0.95
Low HDI	38,839	3.2	5.5	4.48	37,075	3.1	5.3	4.89	0.97	0.96

^*Somalia was excluded in the GLOBOCAN 2022 estimates because HDI for Somalia from the United Nations Development Program (UNDP) was not available. ASR: Age-standardized rate/ratio; HDI: Human development index; MIR: Mortality-to-incidence ratio.

In 2022, 758,725 deaths were estimated worldwide, including 236,899 females and 521,826 males [Table 1]. The ASMRs were 7.4 per 100,000 for all, 4.1 per 100,000 for females, and 10.9 per 100,000 for males. Males had a higher death burden than females, contributing to 68.78% of the total cases. Almost 47.91% of liver cancer-related deaths occurred in Eastern Asia, with an ASMR of 11.9 per 100,000. The highest ASMR was recorded in Northern Africa (13.7 per 100,000), followed by Southeastern Asia, Eastern Asia, and Micronesia, while the lowest ASMR was recorded in South-Central Asia (2.9 per 100,000).

Globally, the age-standardized MIR was 0.86 for both sexes, 0.85 for females, and 0.86 for males [Table 1]. Polynesia (0.99) and North America (0.66) had the highest and lowest ratios, respectively. As the HDI levels increased, the MIRs gradually decreased, ranging from 0.76 to 0.96.

Liver cancer incidence, mortality, and MIR in 2022, by continents

Asia accounted for the majority incidence of liver cancer cases (70.12%) with an ASIR of 10.0 per 100,000 [Table 2]. Globally, the ASIR was the highest in Asia and Africa (8.5 per 100,000), with the two regions comprising approximately 78.65% of all cases worldwide. Among the individual countries, Mongolia exhibited the highest ASIR (96.1 per 100,000), remarkably surpassing that of the other countries [Table 2 and Figure 1A]. China alone contributed to approximately 42.45% of the world’s liver cancer cases. Regarding sex disparities, the ASIRs were consistently higher among males than among females in the selected countries, except for Peru [Figure 2A]. Notably, the incidence in males in Vietnam was 4.26 times higher than that in females. The highest ASIR was observed in the ≥75 years group, especially in Asia, and the lowest was recorded in North America [Figure 3A].

Table 2.

Estimated global incidence, mortality, and MIR of liver cancer by selected countries, in 2022.

Country	New cases	Incidence (per 100,000)		Percent (%)	Liver cancer-related death cases	Mortality (per 100,000)		Percent (%)	Mortality-to-incidence ratio
		Crude rate	ASR (World)			Crude rate	ASR (World)		Crude rate	ASR (World)
Asia	607,361	13.1	10.0	70.12	530,928	11.4	8.7	69.98	0.87	0.87
China	367,657	26.0	15.0	42.45	316,544	22.4	12.6	41.72	0.86	0.84
India	38,703	2.8	2.7	4.47	36,953	2.6	2.6	4.87	0.93	0.96
Indonesia	23,805	8.5	8.0	2.75	23,383	8.4	7.9	3.08	0.99	0.99
Japan	41,388	33.0	9.2	4.78	26,420	21.0	4.3	3.48	0.64	0.47
Korea, Republic of	14,791	28.8	13.7	1.71	12,595	24.5	10.7	1.66	0.85	0.78
Korea, Democratic People Republic of	6180	23.8	16.4	0.71	5791	22.3	15.3	0.76	0.94	0.93
Mongolia	2668	79.0	96.1	0.31	2164	64.1	80.2	0.29	0.81	0.83
Thailand	27,936	39.9	22.7	3.23	27,143	38.7	22.0	3.58	0.97	0.97
Turkey	5039	5.9	4.7	0.58	4929	5.8	4.4	0.65	0.98	0.94
Viet Nam	24,502	24.8	20.2	2.83	23,333	23.6	19.3	3.08	0.95	0.96
Europe	88,871	11.9	5.1	10.26	79,091	10.6	4.2	10.42	0.89	0.82
France	12,172	18.6	7.8	1.41	10,478	16.0	5.9	1.38	0.86	0.76
Germany	9959	11.9	4.5	1.15	8712	10.4	3.5	1.15	0.87	0.78
Italy	11,886	19.7	6.8	1.37	9606	15.9	4.9	1.27	0.81	0.72
Russian Federation	11,748	8.1	4.3	1.36	11,377	7.8	4.0	1.50	0.96	0.93
United Kingdom	8223	12.0	4.8	0.95	7326	10.7	4.0	0.97	0.89	0.83
Mexico	8603	6.5	5.7	0.99	7673	5.8	5.0	1.01	0.89	0.88
Spain	6428	13.8	6.0	0.74	5584	12.0	4.5	0.74	0.87	0.75
Africa	73,844	5.3	8.5	8.53	70,315	5.0	8.2	9.27	0.94	0.96
Egypt	27,946	26.3	32.0	3.23	26,971	25.4	30.8	3.55	0.97	0.96
Ethiopia	2798	2.3	4.1	0.32	2683	2.2	4.0	0.35	0.96	0.98
Nigeria	4382	2.0	4.2	0.51	4252	2.0	4.1	0.56	1.00	0.98
Somalia	301	1.8	3.7	0.03	296	1.8	3.6	0.04	1.00	0.97
South Africa	2650	4.4	4.9	0.31	2401	4.0	4.5	0.32	0.91	0.92
Morocco	1112	2.9	2.6	0.13	1047	2.8	2.4	0.14	0.97	0.92
Latin America and the Caribbean	42,769	6.4	5.0	4.94	39,351	5.9	4.5	5.19	0.92	0.90
Argentina	2504	5.4	3.7	0.29	2147	4.7	3.1	0.28	0.87	0.84
Brazil	13,599	6.3	4.5	1.57	13,041	6.1	4.3	1.72	0.97	0.96
Colombia	2591	5.0	3.6	0.30	2396	4.7	3.3	0.32	0.94	0.92
Mexico	8603	6.5	5.7	0.99	7673	5.8	5.0	1.01	0.89	0.88
Peru	2068	6.1	4.9	0.24	1809	5.4	4.2	0.24	0.89	0.86
Northern America	48,485	13.0	6.7	5.60	35,075	9.4	4.4	4.62	0.72	0.66
Canada	4974	13.0	5.9	0.57	4130	10.8	4.3	0.54	0.83	0.73
United States of America	43,492	13.0	6.8	5.02	30,931	9.2	4.4	4.08	0.71	0.65
Oceania	4806	11.0	7.5	0.55	3965	9.1	5.7	0.52	0.83	0.76
Australia	3333	12.8	7.2	0.38	2591	9.9	4.8	0.34	0.77	0.67
New Zealand	382	7.8	4.0	0.04	336	6.9	3.3	0.04	0.88	0.83

Countries were selected by the number of new cases of liver cancer. ASR: Age-standardized rate/ratio; MIR: Mortality-to-incidence ratio.

Figure 1.

Country-level liver cancer (A) incidence and (B) mortality rates (world standard, per 100,000 population) by continents, in 2022. Red squares or lines indicate incidence, and blue ones indicate mortality.

Figure 2.

Liver cancer (A) incidence and (B) mortality rates (world standard, per 100,000 population) of selected countries by sex and continent, in 2022.

Figure 3.

Age-specific liver cancer (A) incidence and (B) mortality rates (world standard, per 100,000 population) by continents, in 2022.

Asia accounted for approximately 69.98% of deaths worldwide, with an ASMR of 8.7 per 100,000 [Table 2]. Notably, Africa also had a relatively high ASMR (8.2 per 100,000), accounting for approximately 9.27% of all the cases. At the national level, Mongolia also had the highest ASMR (80.2 per 100,000), and China contributed to approximately 41.72% of liver cancer deaths [Table 2]. The ASMR among males in Vietnam was 4.32 times higher than that among females [Figure 2B]. The highest ASMR was observed in the ≥75 years group, especially in Asia, whereas the lowest was recorded in North America [Figure 3B].

Africa exhibited the highest MIR (0.96) among the five continents, while North America had the lowest (0.66) [Table 2]. Among the selected countries, Indonesia had the highest MIR (0.99) and Japan had the lowest (0.47). African countries had relatively high MIRs ranging from 0.92 to 0.96.

Liver cancer incidence and mortality compared in 2022, by HDI regions

Globally, countries with a high HDI had the highest ASIR (12.3 per 100,000), accounting for approximately 57.23% of total cases [Table 1 and Supplementary Figure 1A, http://links.lww.com/CM9/C117]. Countries with the highest liver cancer ASIR such as Mongolia, Egypt, Vietnam, and China contributed the most to this burden [Supplementary Figure 2A, http://links.lww.com/CM9/C117]. In countries with a very high HDI, males typically had a higher burden than females, with ratios ranging from 2.03 to 3.78. People aged ≥ 75 years had the highest onset risk as the risk increased with age, especially in countries with high HDI levels [Supplementary Figure 3A, http://links.lww.com/CM9/C117].

Globally, countries with high HDI had the highest ASMR (10.7 per 100,000), accounting for approximately 57.73% of the total deaths [Table 1 and Supplementary Figure 1B, http://links.lww.com/CM9/C117]. Countries with a high HDI had significantly higher ASMR than other countries, including Mongolia, Egypt, Vietnam, and China [Supplementary Figure 2B, http://links.lww.com/CM9/C117]. Among the age group, ≥75 years group had the highest death risk in the high HDI regions compared to that in others [Supplementary Figure 3B, http://links.lww.com/CM9/C117].

Correlation between liver cancer incidence, mortality, and MIR with HDI and GNI

For ASIR, very weak negative correlations were found with HDI (r = −0.15, P <0.05) and GNI (r = −0.16, P <0.05) in females [Figure 4A]. For ASMR, similarly weak negative correlations were identified between HDI and GNI for both sexes, with correlation coefficients ranging from –0.20 to –0.16 [Figure 4B]. MIRs had stronger negative correlations with HDI for both sexes (r = −0.60, P <0.05), males (r = −0.56, P <0.05), and females (r = −0.63, P <0.05), as well as with GNI [Figure 4C].

Figure 4.

Relationship between country-specific HDI (left panel), and GNI (right panel) with liver cancer (A) incidence; (B) mortality and (C) MIR, in 2022. GNI: Gross national income; HDI: Human development index; MIR: Mortality-to-incidence ratio.

Discussion

In this study, we present the updated numbers and crude and age-standardized rates of liver cancer incidence and death in 2022 at the global, regional, and country levels. We found that: (1) In 2022, there were an estimated 866,136 new cases of liver cancer and 758,725 deaths worldwide, with a global MIR of 0.86. Notably, males exhibited a disproportionately higher burden than females across all levels, with the highest burden observed in the elderly population. (2) Substantial geographic variations in incidence and mortality were observed between and within continents. The regions with the highest incidence rates included Micronesia, Eastern Asia, and Northern Africa, and the regions with the highest mortality rates included Northern Africa, Southeastern Asia, Eastern Asia, and Micronesia. Mongolia exhibited a particularly elevated burden compared with that in other countries. The highest and lowest MIR were recorded in North America and Africa, respectively. (3) We observed significant negative associations between HDI and GNI with ASMR and MIR, irrespective of sex.

Compared to previous findings, the ranks of liver cancer incidence and mortality remain unchanged from 2020.^[15] Liver cancer continues to pose a significant challenge globally, with regional variations in its etiology and risk profiles. In China and East Asia, chronic hepatitis B virus (HBV) infection and aflatoxin contamination of food are prominent risk factors for liver cancer. Conversely, countries such as Egypt and Japan are characterized by chronic hepatitis C virus (HCV) infection as the primary cause. In high-HDI regions such as North America and Western Europe, factors such as chronic HCV infection, alcohol overconsumption, excess body fat, and type 2 diabetes may be more prominent contributors to liver cancer.^[16,17] In sub-Saharan Africa, HBV remains the leading risk factor for liver cancer, and the additional risk posed by co-exposure to aflatoxin-contaminated foods further exacerbates the disease burden.^[18] Given the strong synergistic effect of HBV and aflatoxins on liver cancer development, reducing Aspergillus flavus proliferation might be an effective measure in low- and middle-income countries (LMICs), which could involve improving crop storage and drying methods, particularly for maize and groundnuts.^[19] Moreover, non-viral liver cancer cases are increasing in parallel with rising obesity prevalence, and non-alcoholic fatty liver disease (NAFLD) gradually and more prominently contributes to the development of liver cancer.^[2,20] NAFLD-related liver cancer will continue to increase over the next decade, even in developing regions such as sub-Saharan Africa.^[21]

Mongolia stands out for its strikingly high incidence and mortality rates compared to other countries. High rates of HBV and HCV infection, or co-infection of HBV with HCV or hepatitis D virus (HDV), along with alcohol consumption, have contributed to this heavy burden.^[22] Moreover, Mongolia exhibited unique molecular driver mutations related to HDV infection compared to other regions.^[23] With the HBV vaccination and anti-viral treatment promotion, as well as the reduction in aflatoxin exposure, liver cancer incidence rates have decreased in many high-risk countries such as China, Japan, and the Republic of Korea.^[24] In the United States, the incidence of liver cancer has stabilized after a long history of increasing incidence.^[25] A retrospective analysis of adults aged 35–69 years in the UK found that liver cancer incidence and mortality increased from 1993 to 2018 (annual average percentage change [AAPC]: 3.87% and 2.74%, respectively), with nearly one in two cases attributable to modifiable risk factors.^[26]

The World Health Organization (WHO) has set global targets for reducing hepatitis infections and related-deaths by 90% and 65% by 2030, respectively. By the end of 2022, it is estimated that the hepatitis B vaccine for infants will be introduced in 190 nations, with a global coverage of 84%.^[27] However, the coverage and vaccination schedule also vary among countries, as approximately 113 countries introduced nationwide administration of one dose of the hepatitis B vaccine to newborns within the first 24 h of life, which could efficiently protect against mother-to-child transmission.^[28] In regions with high infection rates such as Africa, the introduction of routine hepatitis B vaccination is limited. In 2022, only 18% of African infants received birth doses.^[28] To address this, the WHO expanded the eligibility for antiviral prophylaxis in pregnant women to prevent mother-to-child transmission of HBV in 2024 new guidelines. In particular, vaccination will be offered at low out-of-pocket costs in low-HDI regions, given the high burden of viral infections.^[29] HCV infection can be effectively treated with direct-acting antivirals, and several countries have achieved HCV elimination by 2030.^[30] However, comprehensive screening of the targeted population requires substantial resources, and the risk of reinfection cannot be avoided.^[31] Therefore, prevention measures such as safe injection practices and effective blood management are indispensable.

Although viral infections remain the predominant risk factors for liver cancer, significant barriers persist in lowering its incidence, primarily related to the feasibility of implementing large-scale prevention, screening, and treatment programs. This challenge is particularly pronounced in regions with limited resources, where achieving success is inherently more difficult. Rural areas with large resident populations face additional hurdles in implementing comprehensive outreach strategies for disease prevention and care.^[32] Consequently, addressing disparities in liver cancer care across different regions and territories must be prioritized to improve outcomes on a global scale. Considering the inadequate use and uptake of screening programs for at-risk populations, efforts to bridge the gap between regions with different HDI levels should focus on innovative approaches to healthcare delivery, capacity-building initiatives, and the development of a sustainable healthcare infrastructure.^[2] Additionally, person-centered data monitoring for the high-risk liver cancer population should be considered to support personal health services, including prevention, diagnosis, and treatment interventions.^[33]

The MIR has been used as a valid estimation of survival.^[14] We found that the MIR of liver cancer was relatively higher, revealing its poor prognosis and low survival rates, as it is often diagnosed late in development.^[34] Additionally, the lowest MIR was found in high-development regions, such as North America, and the highest in less developed regions. These variations may result from initiatives such as screening and early diagnosis, treatment familiarity, and surgical and invasive procedures.^[35] However, despite the rapid development of diagnostic and therapeutic techniques, the liver cancer survival rate has ranged from 5% to 30% from 2000 to 2014.^[34] Moreover, advancements in the surgical and systemic therapeutic landscape of liver cancer have increased the complexity of patient management, necessitating a flexible allocation considering personalized oncological staging features.^[36]

Our analyses revealed that both ASMR and MIRs increased as HDI and GNI decreased in patients with liver cancer. These correlations are consistent with previous research findings and underscore the disparities in medical healthcare and preventive measures for liver cancer.^[37,38] Overall, there were large variations among the countries, particularly in LMICs. In addition to racial and ethnic differences, lower socioeconomic status and poverty have been associated with risk factors for liver cancer, such as diabetes, metabolic syndrome, obesity, alcoholism, and viral infections.^[39] Comprehensive screening and treatment initiatives remain inadequate, exacerbating the existing disparities and presenting heightened obstacles for certain populations in obtaining timely diagnoses and providing suitable medical care.^[40] Financial considerations further compound this issue, as the availability, affordability, and accessibility of cancer medicines are limited in LMICs. Addressing this issue requires a multifaceted approach including measures to improve the affordability of treatment for low-income patients. This could involve expanding public insurance schemes and ensuring the inclusion of essential cancer medicines on the national Essential Medicines Lists (EMLs).^[41]

This study presents an updated global liver cancer burden analysis focusing on geographic disparities. These findings underscore the importance of tailored prevention and control strategies that account for geographic disparities in liver cancer burden. However, this study has certain limitations. First, the estimation of liver cancer statistics in countries with low HDI levels may be subject to underreporting or less reliable data compared to countries with high HDI levels, as many LMICs lack high-quality cancer registry data.^[12] Second, ecological fallacy is an inherent limitation of our study’s interpretation of the correlation analyses. We should note that the correlation coefficients for mortality (ranging from 0.16 to 0.20) are not exceptionally high. Therefore, caution should be exercised when extrapolating deductions at an individual level. Third, this study estimated the total burden of liver cancer and could not distinguish between histological types of hepatocellular carcinoma and intrahepatic cholangiocarcinoma. Lastly, this was a cross-sectional study and could not capture the temporal trend variability of the liver cancer burden owing to limitations in data availability within the GLOBOCAN database. Future longitudinal studies concerning the impact of socioeconomic development should be conducted as it is crucial to understand the disparities present in the current state of healthcare delivery.

The current burden of liver cancer incidence and mortality highlights the significant geographic heterogeneity, which is particularly evident across countries with varying HDI levels. Notably, Eastern Asia and Southern Africa have emerged as regions that contribute substantially to the overall global burden of liver cancer. Such disparities between countries or regions characterized by high HDI levels and those with low-to-medium HDI levels highlight the urgent need to prioritize health accessibility and availability to promote health equity.

Acknowledgments

We would like to express our gratitude to the staff of the International Agency for Research, as well as their collaborators for compiling and making these valuable data publicly available.

Funding

This study was supported by a grant from the Capital’s Funds for Health Improvement and Research (No. 2024-1G-4023).

Conflicts of interest

None.

Supplementary Material

cm9-137-2334-s001.pdf ^{(2.9MB, pdf)}